Enantio- and diastereoselective aldol reactions of achiral ethyl and methyl ketones with aldehydes: the use of enol diisopinocampheylborinates

Abstract Enol diisopinocampheylborinates, derived from achiral ethyl and methyl ketones by enolisation in the presence of tertiary amine bases ( i Pr 2 NEt or Et 3 N), undergo enantio- and diastereoselective aldol reactions with aldehydes. The reagents employed, (+)- and (-)-(Ipc) 2 BOTf, are easily prepared in enantiomerically pure form in two steps from (-)- and (+)-α-pinene, respectively. The aldol reaction between ethyl ketones and aldehydes using (+)- or (-)- (Ipc) 2 BOTf/ i Pr 2 NEt in dichloromethane gives, via the derived chiral Z-enol borinates, syn -α-methyl-β-hydroxy ketones in good enantiomeric excess (66-93% ee) and with high diastereoselectivity (>-95%). In contrast, the anti -selective aldol reaction of diethylketone via the isomeric E-enol diisopinocampheylborinate (by enolisation with (-)-(Ipc) 2 BCl) with methacrolein proceeds with negligible enantioselectivity. Use of both the triflate and chloride reagents in the aldol reaction of methyl ketones with aldehydes gives β-hydroxy ketones in moderate enantiomeric excess (53–78% ee) with a reversal in the enantioface selectivity of the aldehyde compared to the corresponding ethyl ketone syn aldol. This variable selectivity is interpreted as evidence for the participation of competing chair and boat transition states. Other chiral dialkylboron triflate reagents investigated led to reduced enantioselectivities in diethylketone-aldehyde aldol reactions.